AURA_CALAK
ID AURA_CALAK Reviewed; 2497 AA.
AC A0A0M4L8I7;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Highly reducing polyketide synthase aurA {ECO:0000303|PubMed:26340065};
DE Short=HR-PKS aurvA {ECO:0000303|PubMed:26340065};
DE EC=2.3.1.- {ECO:0000269|PubMed:26340065};
DE AltName: Full=Aurovertin biosynthesis cluster protein A {ECO:0000303|PubMed:26340065};
GN Name=aurA {ECO:0000303|PubMed:26340065};
OS Calcarisporium arbuscula (Dendryphion arbuscula).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreales incertae sedis; Calcarisporium.
OX NCBI_TaxID=240499;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26340065; DOI=10.1021/jacs.5b07816;
RA Mao X.M., Zhan Z.J., Grayson M.N., Tang M.C., Xu W., Li Y.Q., Yin W.B.,
RA Lin H.C., Chooi Y.H., Houk K.N., Tang Y.;
RT "Efficient biosynthesis of fungal polyketides containing the dioxabicyclo-
RT octane ring system.";
RL J. Am. Chem. Soc. 137:11904-11907(2015).
CC -!- FUNCTION: Highly reducing polyketide synthase (HR-PKS); part of the
CC gene cluster that mediates the biosynthesis of aurovertins, fungal
CC polyketides that exhibit potent inhibition of adenosine triphosphate
CC synthase (PubMed:26340065). Tha biosynthesis starts with the HR-PKS
CC aurA that selects propionate as the starter unit; synthesizes a hexa-
CC ene chain through the repeated functions of the KR and DH domains in
CC the first six iterations; selectively introduces three alpha-methyl
CC substitutions at C4, C6, and C16 using the S-adensylmethionine-
CC dependent cMET; and shuts off KR and DH in the last three iterations to
CC afford a 1,3,5-triketo portion that can undergo intramolecular
CC cyclization to yield the alpha-pyrone intermediate (PubMed:26340065).
CC AurE may act as a cyclase and enhances the rate of pyrone formation and
CC product release of aurA (PubMed:26340065). The methyltransferase aurB
CC then methylates the C17 hydroxyl group (PubMed:26340065). C17
CC methylation is required to initiate epoxidation by the downstream
CC monooxygenase aurC (PubMed:26340065). The monooxygenase aurC and the
CC epoxide hydrolase aurD can iteratively transform the terminal triene
CC portion of the methylated precursor into the dioxabicyclo[3.2.1]octane
CC scaffold of aurovertin E. Epoxidation modifications of the precursor
CC occur in two separate steps; bis-epoxidation of the two terminal
CC olefins takes place first, followed by another epoxidation that occurs
CC at C7-C8 after tetrahydrofuran formation (PubMed:26340065). The O-
CC acyltransferase aurG converts aurovertin E to aurovertin A
CC (PubMed:26340065). {ECO:0000269|PubMed:26340065}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8A5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y8A5};
CC -!- PATHWAY: Polyketide biosynthesis. {ECO:0000269|PubMed:26340065}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes aurovertin production
CC (PubMed:26340065). {ECO:0000269|PubMed:26340065}.
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DR EMBL; KT581574; ALD83627.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0M4L8I7; -.
DR SMR; A0A0M4L8I7; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2497
FT /note="Highly reducing polyketide synthase aurA"
FT /id="PRO_0000443965"
FT DOMAIN 2409..2487
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 6..440
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 575..896
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 965..1255
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1399..1594
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 2150..2294
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 175
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 669
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 997
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2447
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2497 AA; 272585 MW; 805C6A1E291F3155 CRC64;
MTPEPIAIIG SGCKFPGSST SPSRLWDLIS KPKDVASKPP ADRFNIDGFY HPNPTNLLTT
NAKESYFISE NVRAFDNTFF NIAANEATSL DPQQRLLLET VYESVEAAGL RLEALRGSST
GVFCGVMCAD WEAVVGLDKV VPEYAISGLA RSNLANRISY FFDWNGPSMS IDTACSSSMV
ALHQGITALQ SGECSAVAVI GTNLILTPNL YFAASNVHML SPESRGRMWD HKANGYVRGE
GVASLMLKRL SDAVADGDRI ECVIRASGVN QDGRTLGLTM PSGEAQEKLI RSTYALAGLD
PSRAEDRPQY FEAHGTGTQA GDYQEASGIY NTFFGANPKA SAEEVLHVGS IKTVIGHSEG
CAGLAGLIKA SLCIQHGLIP PNLHFERLNP KLEPYSSHLK VPTALTKWPE LPSGVPRRVS
VNSFGFGGTN SHAILESYEP NLHGTTNGHV NGTSKKTNGL LNGASNLLDS LTNGEESTKP
ALLPFVFSAA SEKTLGALLE KYDSYLGENP NVEAMDLAWS LIQKRSALMY RVTLYAPTIE
GLQSEIQREL ALRKANTPST VISRPDTGKK RILGIFTGQG AQWPQMGLDI ISTFPNARVW
FEELQASLDS LPTAHKPDFS LLEELSAPKP SSRVQEAAVA QPICTAVQIV LVKLLSAIGI
SFDQVVGHSS GEVAAAYAAG VLNAHDAIRI AYLRGRVAHL AGANDKAGGM LAAGLSIEEA
TAFCELPEFA GRIMIAACNS PSSVTLSGDA DAIQEAEKHL KGQDKFARRV LVDTAYHSHH
MEPCSDPYLS AMTGCKIQLG EPTATTWYST VYEGEKPNSS SHANALVGEY WKDNMRNPVL
FYQALMQSIT DAPPSLIVEV GPHPALKGPV LQAISEAVQT NSTIPYISTL SRGATGVKAL
AVTIGSLWTH LGAEGVKVEQ YVALREPSRK LKFIHDLPSY PFDHSQSYWT ETRRSKAYLG
RGPRHELLGD LSEENTEGEW RWRNFLFRSN LEYLEGHQIQ AQTIFPATGY VAMAFEAAGI
MAEGRSMRLV QINDLEIDQA IAFLDDVKGI ETLFRVYQIR SDGNVTNAAF SCHADIGGTL
KTCASGQLVV TWGEMEANLL PSKLPSPSGM SVVDTDEFYA SLGKLGYGYT GLFRGITSLK
RKLNTSSGFL DNVGSEELLL HPSTMDCGLQ CLLAAVGAPG DGELSRLQIP TRIQTTVINP
IFCGKNNVLV GDSLEFEAAV TGLSADGASG DVSLFTRDGP GLIQFEGVHV TPLMQPTASD
DRPMFSEITW GGLLPNAEPL HGPAPPLQFW AGNMDDPQHM CFAVIQEVLS KLTAEDRQRL
EGYRVDVVEW FDHVVEQTRL GENPLCMKEW VDEDPTEALI HLAKTAQPII VEITDVIRKH
FLNFLRGETP MIEVYRQDNL LTRFYDQEQE LKYMSLRVGD VAGQLAFRYP RMKILEIGAG
TGSATRAVLG RIGQYFHSYT FTDISAGFFE DAEATFTEYA DRMVYRVLDI EQDPTGQGFD
ANSYDLVIAA NVLHATKYLE PTMNNVRRLL KPGGHLIALE ITNEHILQDA LLFSAFEGWW
LGKHDNRPWG PKISVPKWEE LLRKTGFGGV QSILPAPEKT EYSFWGYSTF VTQAINDRLE
QLSEPSASDP ATSIISTSDS SEKFGTLMII GGVTDKTSYL VPALKKLLAP SFERIIHTLT
IDSIEYQDAS LAAALCLADM DVPTFQDLTD NKISCLKRLL EVGRRLLWVT AGSESENPYL
SMSKGFLSCI GYEYEGSIHQ YLNIVDPEAV NAQILSTTLM RMLLSDSTND YSLSTGVGSI
ELELRLEDNV MKIPRIMNAT PLNHRYAAGQ RAVYSQADLE KSTVQIRSVQ GNLEFFEGPV
EGSTETQLDQ GQSTIPVHVR YSASLALKVQ NGGFLNLVLG THEVSNVRLI AFSDNNASRV
SVPSALCWEL TNNIAEDQEA QFLNIMASAV LARNIIQTAS TNTSLLVHEA NDALRHAIWT
QAVAKGVQPY FSTSDTSKKQ SNSSTLVFHE TSSTRALARI LPTGLSVIAN FGKAAPNGVM
AKIKPLLSPD VTQEDTGTLY RVSPLLSKGF NLDEVTQTFK VSRIVATEVM HSLANNFAAV
HGETNVISID KLSGRDAKTG ELEILDWTQA RELPVRVSSA SSQVKLSASK TYLLVASRTP
KVEPQWLDEM SRLGARVRIE PMDVTDRESI LSVDRTIRRT LPPIGGVVNG AMVLQDRMFA
DATLDNILGT YKPKVQGSRL LEDIYGDEDL DFFILFGSAT AILGNMGQSS YGAATNFMRS
LIRGRRERNL VGSIIHPAEV RGVGYISRMG IELSRLMNKL VGSHIVSEKD LHETFAEAIL
AGKPASGRNP EVISGFNQHD PEEIPDLIWY SNPETWPLVN YRLQSTTSQS TSTLMPIKQQ
LESATSLAEA AELVLIALNA KIVQKLHLSE DTHMTPDTRL AELGADSLVA VDLRTWFIRE
LDVEIPILQI QSGASIGDLA NSATSKISDS LIPNVKR
